Dystonia is a neurologic movement disorder characterized by sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures or positions. Almost all dystonic movements share a directional quality that is typically sustained. Movements may be prolonged or occur in an instant. In general, dystonia may be classified based on: the age at which symptoms appear; the area or areas of the body that are affected (anatomical distribution); or the cause of the dystonia.
Cervical dystonia, the most common form of focal dystonia, is characterized by abnormal squeezing and twisting muscle contractions in the head and neck area. The dystonic muscle spasms associated with cervical dystonia (CD) may affect any combination of neck muscles. Sustained muscle contractions result in abnormal positions or posturing of the head and neck which results in considerable pain and discomfort. Periodic or patterned spasms result in jerky head movements or periodic or sustained unnatural positioning of the head (dystonic posturing). Sideways or lateral rotation of the head and twisting of the neck is likely the most common finding in CD. This is known as rotational cervical dystonia. In addition, tilting of the head is often present.
Cervical dystonia may begin in the neck and spread into the shoulders, but the symptoms usually plateau and remain stable within five years of onset. This form of focal dystonia is unlikely to spread beyond the neck and shoulders or become generalized dystonia. Occasionally, people with cervical dystonia develop other focal dystonias.
Cervical dystonia may be primary (meaning that it is the only apparent neurological disorder, with or without a family history) or be brought about by secondary causes such as physical trauma. Cases of inherited cervical dystonia may occur in conjunction with early-onset generalized dystonia, which is associated with the DYT1 gene.
Muscle hypertrophy is present in almost all CD patients. Over two-thirds or up to 80% of patients have associated neck pain. About 33% to 40% of these patients also experience head tremor (i.e., dystonic tremor), hand tremor, or both. Approximately 20% of patients with CD also have blepharospasm or dystonia in other muscles or in muscle groups of the arm or hand. In addition, about 15% of patients have hand tremor resembling essential tremor.
Medical therapies are available for treating dystonia including cervical dystonia, but not all patients get adequate relief. DBS is a surgical procedure that interrupts neuronal circuits in the globus pallidus interna (Gpi) and subthalamic nucleus (STN)—areas of the basal ganglia of the brain that do not work correctly in patients with dystonia. This may lessen patients' symptoms and pain but results in decreased movement. Another treatment is regular botulinum toxin injections to the affected muscle, however, this can result in weakness in the muscle at the site of injection, muscle soreness throughout the body, difficulty swallowing, breathing or talking, double vision and/or hoarseness for several days. In addition, high and frequent doses of botulinum toxin could be fatal as botulinum toxin is made of the same bacterium that causes food poisoning. Also, some oral medications have demonstrated some benefit including anticholinergic drugs such as Artane® (trihexyphenidyl) and Cogentin® (benztropine); dopaninergic drugs such as Sinemet® or Madopar® (levodopa), Parlodel® (bromocriptine), and Symmetrel® (amantadine); and GABAergic drugs such as Valium® (diazepam). However, these medications can have undesirable side effects including central nervous system side effects such as confusion, drowsiness, hallucination, personality change and memory difficulties, and peripheral nervous system side effects such as dry mouth, blurred vision, urinary retention and constipation.
Another debilitating condition is post-stroke spasticity. This can occur after a stroke as certain muscles may start to contract involuntarily. Post-stroke spasticity is characterized by increased muscle tone and resistance to movement. The increased stiffness contributes to fatigue by forcing stroke survivors to expend much more energy to perform basic activities. Complications of inadequately controlled post-stroke spasticity include pain, contractures and decubiti. Up to 30% of stroke survivors suffer this disabling spasticity. Present medical treatments include the use of pharmaceuticals such as baclofen, diazepam and dantrolene. However, these medications often cause sedation in patients or lethargy. Further, some patients experience confusion.
Another treatment for post-stroke spasticity is the use of botulinum toxin A (“Botox”). However, there are many undesirable side effects that can be experienced with the use of Botox as mentioned above. Undesirable side effects of Botox include having trouble breathing, talking, or swallowing; drooping eyelids; unusual or severe muscle weakness (especially in a body area that was not injected with the medication); problems with vision or depth perception; crusting or drainage from your eyes; severe skin rashes or itching; and/or chest pain or a heavy feeling with pain spreading to the arm or shoulder, a general ill feeling.
A pharmaceutical with minimal side effects that is known to the medical profession for treating spasticity due to brain damage is clonidine, which is widely recognized as an antihypertensive agent that acts as an agonist on the alpha-2-adrenergic receptor and a neural receptor agonist. In general, clonidine, also referred to as 2,6-dichloro-N-2-imidazolidinyldenebenzenamine (C9H9Cl2N3), may be represented by the following chemical structure:

However, to date clonidine has not been widely appreciated as a treatment for conditions such as dystonia and post-stroke spasticity. Thus, there is a need to develop effective formulations of this compound for these applications.